Article thumbnail
Location of Repository

GTP-binding protein βγ subunits mediate presynaptic calcium current inhibition by GABA(B) receptor

By Yoshinao Kajikawa, Naoto Saitoh and Tomoyuki Takahashi

Abstract

A variety of GTP-binding protein (G protein)-coupled receptors are expressed at the nerve terminals of central synapses and play modulatory roles in transmitter release. At the calyx of Held, a rat auditory brainstem synapse, activation of presynaptic γ-aminobutyric acid type B receptors (GABA(B) receptors) or metabotropic glutamate receptors inhibits presynaptic P/Q-type Ca(2+) channel currents via activation of G proteins, thereby attenuating transmitter release. To identify the heterotrimeric G protein subunits involved in this presynaptic inhibition, we loaded G protein βγ subunits (Gβγ) directly into the calyceal nerve terminal through whole-cell patch pipettes. Gβγ slowed the activation of presynaptic Ca(2+) currents (I(pCa)) and attenuated its amplitude in a manner similar to the externally applied baclofen, a GABA(B) receptor agonist. The effects of both Gβγ and baclofen were relieved after strong depolarization of the nerve terminal. In addition, Gβγ partially occluded the inhibitory effect of baclofen on I(pCa). In contrast, guanosine 5′-O-(3-thiotriphosphate)-bound G(o)α loaded into the calyx had no effect. Immunocytochemical examination revealed that the subtype of G proteins G(o), but not the G(i), subtype, is expressed in the calyceal nerve terminal. These results suggest that presynaptic inhibition mediated by G protein-coupled receptors occurs primarily by means of the direct interaction of G(o) βγ subunits with presynaptic Ca(2+) channels

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 2001
DOI identifier: 10.1073/pnas.141031298
OAI identifier: oai:pubmedcentral.nih.gov:35466
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://dx.doi.org/10.1073/pnas... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.